CBFA2T3::GLIS2-positive acute leukemia with RAM and mixed T/megakaryocytic phenotype.

Herein, we present a rare case of acute myeloid leukemia (AML) with CBFA2T3-rearrangement and the expression of megakaryocytic and lymphoid markers, highlighting the need for a high suspicion index in differential diagnosis and applying adequate workup to avoid misdiagnosing this entity. CBFA2T3::GLIS2-positive AML is primarily found in infants with non-down syndrome acute megakaryoblastic leukemia (non-DSAMKL). Flow cytometry immunophenotyping plays an important role in recognizing the unique immunophenotype of bright CD56 expression with dim/negative expression of HLA-DR, CD38, and CD45 termed the RAM immunophenotype in this entity. Still, CBFA2T3::GLIS2-positive acute leukemia with T/megakaryocytic markers could be misdiagnosed as T-lymphoblastic leukemia/lymphoma, early T-cell precursor acute lymphoblastic leukemia/lymphoma, NK lymphoblastic leukemia, AML with minimal differentiation, or AML with myelodysplasia-related changes.

Intraoperative blood collection without fluid replacement for cardiac surgery - A retrospective analysis.

Background: Transfusion rates in cardiac surgery are high. Aim: To determine if intraoperative autologous blood removal without volume replacement is associated with fewer homologous blood transfusions without increasing acute kidney injury. Setting and Design: Retrospective, comparative study. Materials and Methods: Adult patients undergoing cardiac surgery, excluding those who underwent ventricular assist device surgery, heart transplants, or cardiac surgery without cardiopulmonary bypass were excluded, who had 1-3 units of intraoperative autologous blood removal were compared to patients without blood removal for determination of volume replacement, vasopressor support, acute kidney injury, and transfusions. Results: Autologous blood removal was associated with fewer patients receiving homologous transfusions: intraoperative red cell transfusions fell from 75% (Control) to 48% (1 unit removed), 40% (2 units), and 30% (3 units), P < 0.001. Total intraoperative and postoperative homologous RBC units transfused were lower in the blood removal groups: median (interquartile range) 3 (1, 6) in Control patients and 0 (0, 2), 0 (0, 2) and 0 (0, 1) in the 1, 2, and 3 units removed groups, P < 0.001. Similarly, plasma, platelet, and cryoprecipitate transfusions decreased. After adjustment for confounders, increased amounts of autologous blood removal were associated with increased intravenous fluids, only when 2 units were removed, and trivially increased vasopressor use. However, it was not associated with acidosis or acute kidney injury. Conclusions: Intraoperative autologous blood removal without volume replacement of 1-3 units for later autologous transfusion is associated with decreased homologous transfusions without acidosis or acute kidney injury.

Impact of a Rapid-Access Ambulatory Psychiatry Encounter on Subsequent Emergency Department Utilization.

The authors sought to determine whether providing a rapid-access ambulatory psychiatry encounter correlated with emergency department utilization during a 6-month follow-up period. Electronic medical records of patients who accessed ambulatory psychiatric care through an urgent care psychiatry clinic that offers treatment exclusively on a walk-in basis over a 1-year period (N = 157) were reviewed retrospectively to track emergency department encounters with and without a psychiatric chief complaint in the 6 months before and after the initial psychiatry evaluation. Among patients who had not previously received ambulatory psychiatric care (N = 88), emergency department utilization decreased from 0.68 visits per patient to 0.36, and this difference was statistically significant (p = 0.0147). No statistically significant differences were found between the average number of emergency department encounters in the 6 months before and after the rapid-access ambulatory psychiatry encounter, regardless of chief complaint, when all patients were included in the analysis. Providing a rapid-access ambulatory psychiatry encounter may reduce subsequent emergency department utilization among patients who have not previously received ambulatory psychiatric care.

A Successful Walk-In Psychiatric Model for Integrated Care.

PURPOSE: Accommodating walk-in psychiatry visits in primary care can improve access to psychiatric care for patients from historically underserved groups. We sought to determine whether a walk-in psychiatry model embedded within an integrated care practice could be sustained over time, and to characterize the patients who accessed care through it. METHODS: We reviewed electronic health records linked to 811 psychiatry encounters in an integrated care practice between October 1, 2015 and September 30, 2017. Primary outcomes were the initial and return psychiatry encounters per month. Secondary outcomes were the demographics and diagnoses of patients who accessed their initial visits through walk-in sessions and scheduled appointments. RESULTS: 490 initial psychiatry evaluations and 321 return encounters took place over the 2-year study period. The volume of initial psychiatry evaluations per month did not significantly change, but the volume of psychiatry follow-up encounters significantly increased after the walk-in session expanded. Medicaid recipients (OR, 1.9; 95% CI, 1.2 to 3.0); individuals without a college degree (OR, 1.7; 95% CI, 1.1 to 2.5); individuals who were single, divorced, or separated (OR, 1.7; 95% CI, 1.1 to 2.5); and individuals who identified as Black or Hispanic (OR, 2.5; 95% CI, 1.7 to 3.6) were more likely to access an initial psychiatry evaluation through a walk-in session as opposed to a scheduled appointment. CONCLUSIONS: Providing psychiatric care on a walk-in basis in integrated care is sustainable. Patients from historically underserved groups may access psychiatric care disproportionately through a walk-in option when it is available.

Longitudinal Urgent Care Psychiatry as a Unique Access Point for Underserved Patients.

OBJECTIVE: The authors sought to determine whether a walk-in psychiatry model with longitudinal follow-up capability could improve access for patients who traditionally miss appointments. METHODS: An urgent care clinic that offers treatment exclusively on a walk-in basis was opened within an adult psychiatry practice to accommodate patients who missed prior scheduled appointments. Electronic health records for patients who received an initial psychiatry evaluation at the practice during a 6-month period (N=355) were reviewed retrospectively to track the clinic's productivity and patient demographic characteristics. RESULTS: Eighty patients (23%) accessed their initial psychiatry encounters through the walk-in clinic. Medicaid recipients (odds ratio [OR]=1.89, 95% confidence interval [CI]=1.10-3.24) and individuals without a college degree (OR=1.86, 95% CI=1.04-3.32) were more likely than patients with other insurance carriers and those with a college degree, respectively, to access care through a walk-in encounter versus a scheduled appointment. CONCLUSIONS: Longitudinal walk-in psychiatry services can feasibly be offered through the longitudinal urgent care psychiatry model. This model may serve as a unique access point for patients from historically underserved groups.

Widespread occurrence of the amphibian chytrid fungus Batrachochytrium dendrobatidis in the southeastern USA.

From 1999 to 2006, we sampled > 1200 amphibians for the fungal pathogen Batrachochytrium dendrobatidis (Bd) at 30 sites in the southeastern USA. Using histological techniques or PCR assays, we detected chytrid infection in 10 species of aquatic-breeding amphibians in 6 states. The prevalence of chytrid infection was 17.8% for samples of postmetamorphic amphibians examined using skin swab-PCR assays (n = 202 samples from 12 species at 4 sites). In this subset of samples, anurans had a much higher prevalence of infection than caudates (39.2% vs. 5.5%, respectively). Mean prevalence in ranid frogs was 40.7%. The only infected salamanders were Notophthalmus viridescens at 3 sites. We found infected amphibians from late winter through late spring and in 1 autumn sample. Although we encountered moribund or dead amphibians at 9 sites, most mortality events were not attributed to Bd. Chytridiomycosis was established as the probable cause of illness or death in fewer than 10 individuals. Our observations suggest a pattern of widespread and subclinical infections. However, because most of the sites in our study were visited only once, we cannot dismiss the possibility that chytridiomycosis is adversely affecting some populations. Furthermore, although there is no evidence of chytrid-associated declines in our region, the presence of this pathogen is cause for concern given global climate change and other stressors. Although presence-absence surveys may still be needed for some taxa, such as bufonids, we recommend that future researchers focus on potential population-level effects at sites where Bd is now known to occur.

Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8.

Nrdp1 is a RING finger-containing E3 ubiquitin ligase that physically interacts with and regulates steady-state cellular levels of the ErbB3 and ErbB4 receptor tyrosine kinases and has been implicated in the degradation of the inhibitor-of-apoptosis protein BRUCE. Here we demonstrate that the Nrdp1 protein undergoes efficient proteasome-dependent degradation and that mutations in its RING finger domain that disrupt ubiquitin ligase activity enhance stability. These observations suggest that Nrdp1 self-ubiquitination and stability could play an important role in regulating the activity of this protein. Using affinity chromatography, we identified the deubiquitinating enzyme USP8 (also called Ubpy) as a protein that physically interacts with Nrdp1. Nrdp1 and USP8 could be coimmunoprecipitated, and in transfected cells USP8 specifically bound to Nrdp1 but not cbl, a RING finger E3 ligase involved in ligand-stimulated epidermal growth factor receptor down-regulation. The USP8 rhodanese and catalytic domains mediated Nrdp1 binding. USP8 markedly enhanced the stability of Nrdp1, and a point mutant that disrupts USP8 catalytic activity destabilized endogenous Nrdp1. Our results indicate that Nrdp1 is a specific target for the USP8 deubiquitinating enzyme and are consistent with a model where USP8 augments Nrdp1 activity by mediating its stabilization.

Effect of inhibitors of nitric oxide synthase on acetaminophen-induced hepatotoxicity in mice.

We recently reported that following a toxic dose of acetaminophen to mice, tyrosine nitration occurs in the protein of cells that become necrotic. Nitration of tyrosine is by peroxynitrite, a species formed from nitric oxide (NO) and superoxide. In this manuscript we studied the effects of the NO synthase inhibitors N-monomethyl-l-arginine (l-NMMA), N-nitro-l-arginine methyl ester (NAME), l-N-(1-iminoethyl)lysine (l-NIL), and aminoguanidine on acetaminophen hepatotoxicity. Acetaminophen (300 mg/kg) increased serum nitrate/nitrite and alanine aminotransferase (ALT) levels, indicating increased NO synthesis and liver necrosis, respectively. None of the NO synthase inhibitors reduced serum ALT levels. In fact, l-NMMA, l-NIL, and aminoguanidine significantly augmented acetaminophen hepatotoxicity at 4 h. A detailed time course indicated that aminoguanidine (15 mg/kg at 0 h and 15 mg/kg at 2 h) significantly increased serum ALT levels over that for acetaminophen alone at 2 and 4 h; however, at 6 and 8 h serum ALT levels in the two groups were identical. At 2 h following acetaminophen plus aminoguanidine NO synthesis was significantly increased; however, at 4, 6, and 8 h NO synthesis was significantly decreased. Aminoguanidine also decreased acetaminophen-induced nitration of tyrosine. Acetaminophen alone did not induce lipid peroxidation, but acetaminophen plus aminoguanidine significantly increased hepatic lipid peroxidation (malondialdehyde levels) at 2, 4, and 6 h. These data are consistent with NO having a critical role in controlling superoxide-mediated lipid peroxidation in acetaminophen hepatotoxicity. Thus, acetaminophen hepatotoxicity may be mediated by either lipid peroxidation or by peroxynitrite.